Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study.

BACKGROUND: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM. METHODS AND FINDINGS: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005-2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4-3.8, p<0.001) than men (2.3: 2.0-2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2-3.0, p<0.001) in men and 2.7 (2.2-3.4, p<0.001) in women. Between 2005-2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60-69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA(1c) of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used. CONCLUSIONS: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed. Please see later in the article for the Editors' Summary.

Voltage-gated potassium channel antibody-related encephalopathy: a case which may extend the documented phenotype of this condition.

A 51-year-old man presented with a focal epileptic, fluctuating encephalopathy. Antibodies to voltage-gated potassium channels (VGKC-Abs) were detected in his serum. Several features of this case were different from those previously reported in VGKC-Ab-associated encephalitis, illustrating that it may have a broader phenotype than previously documented. These features were: excess hepatic iron deposits without cirrhosis, reduced consciousness and fluctuating neurological signs. Previous history included personality change, depression, type 2 diabetes mellitus, pupil sparing third nerve palsy and epilepsy secondary to a head injury. He had never drunk alcohol and had recovered from a similar episode 4 years previously. Both episodes resolved after approximately 2 months. The cerebrospinal fluid had a raised protein content but no organisms. The patient was heterozygous for C282Y and negative for H63D mutations excluding classical idiopathic haemochromatosis. He recovered with supportive care to his premorbid level of health.

Rennies, Crohn's disease and severe hypercalcaemia.

A 59-year-old lady presented with vomiting and diarrhoea. She was found to have severe hypercalcaemia (5.2 mmol/l) and to be in renal failure. She had a high daily intake of calcium carbonate in the form of Rennies Dual Action, raising the possibility of milk-alkali syndrome. She had ongoing gastrointestinal symptoms after resolution of hypercalcaemia. Further investigation revealed, previously undiagnosed rectal Crohn's disease. Serum 1,25-dihydroxyvitamin D (calcitriol) level was markedly elevated. It is possible that the calcitriol from Crohn's disease tissue facilitated excessive absorption of calcium from the antacid preparation, thus triggering hypercalcaemia.

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.

OBJECTIVE: To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease. DESIGN: Multicentre, randomised, double blind, 2x2 factorial, placebo controlled trial. SETTING: 16 hospital centres in Scotland, supported by 188 primary care groups. PARTICIPANTS: 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. INTERVENTIONS: Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318). MAIN OUTCOME MEASURES: Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. RESULTS: No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89). CONCLUSION: This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53295293.

TIMI Risk Score predicts early readmission.

AIM: To assess if the TIMI Risk Score could predict early readmission. PARTICIPANTS: 869 consecutive admissions to a Scottish district general hospital with suspected acute coronary syndrome. METHODS: A computerised clinical information system was interrogated to verify readmission. Area under the receiver operator characteristic curve and chi-square test for trend between TIMI Risk Score and readmission rate were calculated. RESULTS: Median follow up was 73 days. There was a strong association between TIMI Risk Score and readmission rate (chi-square test for trend, p<0.001), with an area under the receiver operator characteristic curve of 0.60 (95% C.I. 0.55-0.65). CONCLUSION: The TIMI Risk Score can predict readmission. This study reinforces its utility as a tool for identifying patients more likely to benefit from aggressive intervention.

Age-dependent differences in presentation, risk factor profile, and outcome of suspected acute coronary syndrome.

OBJECTIVES: To compare the presenting complaint, risk factors, and outcome of suspected acute coronary syndrome (ACS) in those aged 65 and older with those of a younger cohort. DESIGN: Prospective observational cohort study. SETTING: A typical Scottish district general hospital covering a population of 150,000. PARTICIPANTS: Patients presenting with suspected ACS (N=869) over a 6-month period. MEASUREMENTS: Main presenting complaint and major risk factors including electrocardiogram (ECG) changes. Primary outcome measures were percutaneous coronary intervention, recurrent myocardial infarction, and death at 3-month follow-up. RESULTS: Four hundred seventy-seven (55%) were aged 65 and older. Older patients were less likely to present with chest pain and more likely to present with breathlessness or collapse. They had fewer major risk factors for heart disease. There was a higher proportion with ischemic ECG changes, elevated troponin, and major acute coronary events at follow-up. Older patients were less likely to be accepted for angiography even though they were more likely than the younger cohort to have significant coronary artery disease when angiography was performed (chi-square test, P<.01 for all above). CONCLUSION: Older patients with suspected ACS were more likely to present atypically and have worse outcomes than their younger counterparts, despite having fewer major risk factors. The results highlight the importance of age as a predictor of adverse outcome and suggest that clinicians need to ensure equitable access to angiography for older patients.

Predicting vascular risk in Type 1 diabetes: stratification in a hospital based population in Scotland.

AIMS: To estimate the absolute cardiovascular risk of patients with Type 1 diabetes attending hospital diabetes clinics in Scotland and to develop a method for identifying those at highest risk, thus enabling therapy to be targeted. METHODS: Baseline information was collected for 2136 patients with Type 1 diabetes using the Royal College of Physicians of Edinburgh Diabetes Register. These records were then linked to diagnoses of macrovascular disease in databases of the Information Statistics Division of the Common Services Agency. RESULTS: During six to nine years of follow up 110 patients (5%) developed macrovascular disease. There were significant associations between baseline age (P < 0.00001), blood pressure (P < 0.00001), albuminuria (P < 0.0002), HbA1c (P < 0.001), cholesterol (P < 0.00001) and smoking status (P < 0.00001) with the development of macrovascular disease. A scoring system for future macrovascular risk was developed from a multivariate analysis of this data. CONCLUSIONS: The data confirm the high vascular risk of patients with Type 1 diabetes. The relationship with age is such that those patients above 50 years require only one additional risk factor to reach such a high vascular risk that intervention is indicated. Using these data many patients between the age of 40 and 49 years are also likely to be identified to be at high risk.

Can we see more outpatients without more doctors?

A reduction in the number of return patients attending general cardiology clinics, if achievable without harm, would improve access for newly referred patients. Outpatient clinic letters (525) sent to general practitioners over a three-month period were reviewed. Simultaneously, physicians' opinions were collected by questionnaire. A subset of 30 clinic patients who attended three local general practitioners were studied to identify how many were assessed in primary care, and how often, in a six-month period. The hospital records of these patients were reviewed to determine whether information about these visits to the general practitioner was documented in the hospital notes. From the outpatient clinics the discharge rates were only 26% and the reason for further clinic review was often not clear. The fact that many patients had no intervention or treatment change performed at the clinic (42%) indicates that patients are reviewed to assess symptom change rather than to receive further interventions. The use of fixed times for review appointment (six months or 1 year) suggests that the intervals are determined by habit rather than clinical indication. A high proportion of patients (28/30) were reviewed at least once in primary care by general practitioners between hospital clinic visits and 20/30 were seen three or more times. There was poor documentation of these consultations in the hospital case notes, and so hospital physicians may be unaware that symptoms are under regular review in primary care. This study suggests that a substantial proportion of current cardiology return outpatients do not require regular outpatient review. However, alternative management demands good communication and exchange of information between secondary and primary care, development of formal written discharge planning in outpatient letters and other forms of follow-up.